NEUROPATHOLOGY CORE ? CORE D: PROJECT SUMMARY/ABSTRACT Postmortem examination remains critical to elucidate the etiology in cases of dementia and to confirm the diagnosis of AD, despite recent advances in neuroimaging and fluid biomarkers. Autopsy is also critical for confirming the clinical diagnosis and identifying comorbidities, which are common in older subjects. The Neuropathology Core (Core D) of the Johns Hopkins Alzheimer's Disease Research Center (JHADRC) has three overarching goals. The first is to conduct postmortem neuropathological assessments in subjects enrolled in the JHADRC Clinical Core. Second, to prepare, store, and distribute autopsy brain tissues for research. The third goal is the training of young physicians and neuroscientists in the neuropathology of dementias and neurodegenerative diseases. The specific aims of Core D are as follows: (1) to arrange and perform autopsies on clinically well-characterized subjects enrolled through the JHADRC and assist with consensus diagnoses on JHADRC subjects, (2) to store optimally prepared tissues from the autopsies and to make these specimens available to investigators associated with the JHADRC and at other collaborating institutions, (3) to integrate the neuropathologic data from these cases with the clinical and biomarker data acquired in the same participants, using the JHADRC database, and to submit the neuropathology data to the National Alzheimer's Coordinating Center (NACC), working with the Data Core (4) to support the assessment of genetically engineered mouse models relevant to Alzheimer's disease (AD) and related disorders, and (5) to train basic investigators and clinical neuroscientists in the morphological and diagnostic concepts relevant to AD, to other types of dementias and neurodegenerative disorders (including trainees supported by the REC). In addition, the availability of human brain postmortem tissues has become increasingly important for validating research hypotheses and for investigations and development of biomarkers of AD. Core D will therefore be expanding its postmortem tissue collection to include a large number of specimens from younger subjects (30 to 65 years) suitable to examine the very early stages of AD pathology and its pathogenesis.